Watts Gerald F, Ji Juying, Chan Dick C, Ooi Esther M M, Johnson Anthony G, Rye Kerry-Anne, Barrett P Hugh R
Lipoprotein Research Unit, School of Medicine and Pharmacology, University of Western Australia, Perth, WA 6000 Australia.
Clin Sci (Lond). 2006 Sep;111(3):193-9. doi: 10.1042/CS20060072.
The aim of the present study was to investigate the association between changes in apoB (apolipoprotein B-100) kinetics and plasma PLTP (phospholipid transfer protein) and CETP (cholesteryl ester transfer protein) activities in men with MetS (the metabolic syndrome) treated with fenofibrate. Eleven men with MetS underwent a double-blind cross-over treatment with fenofibrate (200 mg/day) or placebo for 5 weeks. Compared with placebo, fenofibrate significantly increased the FCRs (fractional catabolic rates) of apoB in VLDL (very-low-density lipoprotein), IDL (intermediate-density lipoprotein) and LDL (low-density lipoprotein) (all P<0.01), with no significant reduction (-8%; P=0.131) in VLDL-apoB PR (production rate), but an almost significant increase (+15%, P=0.061) in LDL-apoB PR. Fenofibrate significantly lowered plasma TG [triacylglycerol (triglyceride); P<0.001], the VLDL-TG/apoB ratio (P=0.003) and CETP activity (P=0.004), but increased plasma HDL (high-density lipoprotein)-cholesterol concentration (P<0.001) and PLTP activity (P=0.03). The increase in PLTP activity was positively associated with the increase in both LDL-apoB FCR (r=0.641, P=0.034) and PR (r=0.625, P=0.040), and this was independent of the fall in plasma CETP activity and lathosterol level. The decrease in CETP activity was positively associated with the decrease in VLDL-apoB PR (r=0.615, P=0.044), but this association was not robust and not independent of changes in PLTP activity and lathosterol levels. Hence, in MetS, the effects of fenofibrate on plasma lipid transfer protein activities, especially PLTP activity, may partially explain the associated changes in apoB kinetics.
本研究的目的是调查非诺贝特治疗的代谢综合征(MetS)男性患者载脂蛋白B(apoB,即载脂蛋白B-100)动力学变化与血浆磷脂转运蛋白(PLTP)及胆固醇酯转运蛋白(CETP)活性之间的关联。11名患有MetS的男性接受了非诺贝特(200毫克/天)或安慰剂的双盲交叉治疗,为期5周。与安慰剂相比,非诺贝特显著提高了极低密度脂蛋白(VLDL)、中间密度脂蛋白(IDL)和低密度脂蛋白(LDL)中apoB的分解代谢率(FCRs)(均P<0.01),VLDL-apoB生成率(PR)无显著降低(-8%;P=0.131),但LDL-apoB PR几乎显著增加(+15%,P=0.061)。非诺贝特显著降低了血浆甘油三酯(TG)[三酰甘油(甘油三酯);P<0.001]、VLDL-TG/apoB比值(P=0.003)和CETP活性(P=0.004),但提高了血浆高密度脂蛋白(HDL)胆固醇浓度(P<0.001)和PLTP活性(P=0.03)。PLTP活性的增加与LDL-apoB FCR(r=0.641,P=0.034)和PR(r=0.625,P=0.040)的增加呈正相关,且这与血浆CETP活性和羊毛甾醇水平的下降无关。CETP活性的降低与VLDL-apoB PR的降低呈正相关(r=0.615,P=0.044),但这种关联并不稳健,且不独立于PLTP活性和羊毛甾醇水平的变化。因此,在MetS中,非诺贝特对血浆脂质转运蛋白活性,尤其是PLTP活性的影响,可能部分解释了apoB动力学的相关变化。